Transcriptional modulation of mitochondria biogenesis pathway at and above critical speed in mice.

High- or moderate-intensity endurance training leads to mitochondrial biogenesis via the peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α)/mitochondrial transcription factor A (Tfam) signaling pathway. Although this pathway is stimulated during acute exercise, the relationship between its activity and the intensity of the exercise has not been characterized. In animal studies, individualized running speeds have not previously been assessed. Here, we sought to determine whether this pathway was modulated after a bout of exhaustive exercise at different relative intensities (at and over critical speed (CS)). Our starting hypotheses were that (i) exercise-induced overexpression of PGC-1α in skeletal muscle falls at intensities above CS, and (ii) transcriptional activity of the mitochondrial biogenesis signaling cascade is intensity-sensitive at and above CS. To test these hypothesis, male Friend Virus B-Type mice were divided into a control group and three exercise groups (exercising at CS, peak velocity (vPeak) and 150 % CS, respectively). mRNA expression levels for genes involved in mitochondrial biogenesis signaling were analyzed in the quadriceps muscle. PGC-1α was overexpressed at all exercise intensities. We also identified that, PGC-1α mRNA expression was negatively correlated with exercise intensity and blood lactate levels but not with maximal oxygen uptake, vPeak, or CS. Expression of the PGC-1α co-activator peroxisome proliferator-activated receptor ß was negatively correlated with the exercise intensity. In contrast, expression levels of Tfam were dissociated from exercise intensity. Our data indicate that at the intensities used in endurance training, the expression of mitochondrial biogenesis genes is finely modulated by the relative intensity of exhaustive exercise.

Dietary intakes and antioxidant status in mind-body exercising pre- and postmenopausal women.

OBJECTIVE: The decline in antioxidant defenses due to both estrogen loss and frequent adoption of poor dietary choices exposes postmenopausal women to cardiovascular diseases. Adequate nutrition and physical exercise are two factors of health promotion. This study investigated whether regular practice of mind-body exercise (yoga and/or tai chi) alters dietary intake and antioxidant status and balances the menopause-related increases in lipid peroxidation and cardiovascular risk. DESIGN: Cross-sectional study. SETTING: The study was conducted in an urban community in Bangkok (Thailand) between May and August 2007. PARTICIPANTS: Premenopausal (Pre M; 39±8 yrs; n=56) and postmenopausal (Post M; 54±5 yrs; n=39) women who had been practicing yoga (Y) and/or tai chi (TC) more than 3 hours/week for a year, or who had no regular physical activity practice (sedentary, S). MEASUREMENTS: All participants completed food frequency questionnaires and 4-day food and activity records. Blood was collected on day 5. Factorial ANOVA tests were performed according to menopause status, exercise, and hormone replacement therapy (HRT) groups. RESULTS: Post M had higher (p = 0.01) dietary fiber intake compared with Pre M. Yoga practitioners had lower BMI (p = 0.004) and lower fat intake (p = 0.02) compared with their S and TC counterparts. Plasma total antioxidant status was significantly and independently lower and higher in Y and Post M groups, respectively. However, no difference was shown after adjusting for BMI. Regardless of menopause status and HRT, the activity of erythrocyte glutathione peroxidase - an aerobic training-responsive enzyme - was higher (p < 0.001) in TC practitioners compared with other groups. No effects were shown on erythrocyte superoxide dismutase activity, plasma lipid peroxidation (TBARS) or total homocysteine concentrations. CONCLUSION: Yoga and tai chi exercises can be used as components of a strategy to promote healthy lifestyles (balanced diet and moderate intensity exercise) in vulnerable populations, such as menopausal women, in order to prevent aging induced oxidative stress-related diseases.

Biomarker-based evaluation of two 24-h recalls for comparing usual fish, fruit and vegetable intakes across European centers in the EFCOVAL Study.

BACKGROUND/OBJECTIVES: A standardized methodology is important to enable consistent monitoring of dietary intake across European countries. For this reason, we evaluated the comparability of the assessment of usual food intake collected with two non-consecutive computerized 24-h dietary recalls (24-HDRs) and a food propensity questionnaire (FPQ) among five European centers. SUBJECTS/METHODS: Two 24-HDRs using EPIC-Soft (the software developed to conduct 24-HDRs in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study) were performed to determine fish, fruit and vegetable (FV) consumed by 600 adults in Belgium (BE), the Czech Republic (CZ), France (FR), the Netherlands (NL) and Norway (NO) in a validation study. An FPQ was used to identify non-consumers. Information from the 24-HDRs and FPQ were used to estimate individual usual food intake by the Multiple Source Method (MSM). Blood samples were drawn to determine fatty acids in phospholipids and serum carotenoids as biomarkers of fish, and FV intake, respectively. RESULTS: The pooled correlation between usual fish intake and eicosapentaenoic acid plus docosahexaenoic acid in phospholipids was 0.19 in men and 0.31 in women (P for heterogeneity >0.50) and center-specific correlations ranged between 0.08 (CZ) and 0.28 (BE and NO) in men, and between 0.19 (BE) and 0.55 (FR) in women. For usual FV intake, the pooled correlation with serum carotenoids was 0.31 in men and 0.40 in women (P for heterogeneity >0.10); the center-specific correlations varied between 0.07 (NO) and 0.52 (FR) in men, and between 0.25 (NL) and 0.45 (NO) in women. CONCLUSION: Two standardized 24-HDRs using EPIC-Soft and an FPQ appeared to be appropriate to rank individuals according to their fish and FV intake in a comparable way among five European centers.

PPARbeta activation induces rapid changes of both AMPK subunit expression and AMPK activation in mouse skeletal muscle.

AMP-activated protein kinases (AMPK) are heterotrimeric, αßγ, serine/threonine kinases. The γ3-AMPK subunit is particularly interesting in muscle physiology because 1) it is specifically expressed in skeletal muscle, 2) α2ß2γ3 is the AMPK heterotrimer activated during exercise in humans, and 3) it is down-regulated in humans after a training period. However, mechanisms underlying this decrease of γ3-AMPK expression remained unknown. We investigated whether the expression of AMPK subunits and particularly that of γ3-AMPK are regulated by the PPARß pathway. We report that PPARß activation with GW0742 induces a rapid (2 h) and sustained down-regulation of γ3-AMPK expression both in mouse skeletal muscles and in culture myotubes. Concomitantly, phosphorylation levels of both AMPK and acetyl-coenzyme A carboxylase are rapidly modified. The γ3-AMPK down-regulation is also observed in muscles from young and adult transgenic mice with muscle-specific overexpression of peroxisome proliferator-activated receptor ß (PPARß). We showed that γ3-AMPK down-regulation is a rapid physiological muscle response observed in mouse after running exercise or fasting, two situations leading to PPARß activation. Finally, using C2C12, we demonstrated that dose and time-dependent down-regulation of γ3-AMPK expression upon GW0742 treatment, is due to decrease γ3-AMPK promoter activity.

Peroxisome proliferator-activated receptor beta activation promotes myonuclear accretion in skeletal muscle of adult and aged mice.

We reported recently that peroxisome proliferator-activated receptor beta (PPARbeta) activation promotes a calcineurin-dependent exercise-like remodelling characterised by increased numbers of oxidative fibres and capillaries. As physical exercise also induces myonuclear accretion, we investigated whether PPARbeta activation alters myonuclear density. Transgenic muscle-specific PPARbeta over-expression induced 14% increase of myonuclear density. Pharmacological PPARbeta activation promoted rapid and massive myonuclear accretion (20% increase after 48 h), which is dependent upon calcineurin/nuclear factor of activated T cells signalling pathway. In vivo bromodeoxyuridine labelling and proliferating cell nuclear antigen immunodetection revealed that PPARbeta activation did not promote cell proliferation, suggesting that the PPARbeta-promoted myonuclear accretion involves fusion of pre-existing muscle precursor cells to myofibres rather than cell division. Finally, we showed that in skeletal muscle, ageing led to a down-regulation of PPARbeta accompanied by decrease of both oxidative fibre number and myonuclear density. PPARbeta pharmacological activation counteracts, at least in part, the ageing-driven muscle remodelling.

Does antioxidant system adaptive response alleviate related oxidative damage with long term bed rest?

OBJECTIVES: The aim of the study was to evidence oxidative damage and erythrocyte antioxidant enzyme activities during long term bed rest (LTBR) and recovery, while verifying the prophylactic effects of resistance exercise on LTBR-induced oxidative damage. DESIGN AND METHODS: 11 healthy male participated in the study. Nutrient intakes were monitored. Assessments occurred during LTBR (60th and 90th day) and 90 days after the end. RESULTS: LTBR induced only a slight decrease in total thiol protein (SH) group concentrations. Glutathione peroxidase (GPx) activity was upregulated during LTBR and down regulated after recovery suggesting that hypokinesia induces an oxidative stress. These effects where not correlated to antioxidant intake as nutritional density is preserved. Lipoperoxidative markers stay unchanged. CONCLUSIONS: Exercise alleviates hypokinesia outcomes by preserving glutathione reductase activity with minor effect on hypokinesia-induced antioxidant response and oxidative stress which both exhibit a high magnitude inter-individual variability. Return to initial physical activity allows biomarkers to return to initial values marking the end of the stress. Hypokinetic situations should be considered as an oxidative stressful situation requiring exercise and nutritional strategies.

Does physical exercise modify antioxidant requirements?

Physical training is known to induce a biochemical adaptive response which might require an increase in the ingestion and/or the absorption of micronutrients. A question that is still being raised is whether acute or chronic exercise modifies antioxidant requirements. First, the present review brings to light the most crucial studies on the topic. Second, it interprets the established relationships between antioxidant micronutrient intakes and the adaptive response of antioxidant systems. Finally, it exposes the major questions connected with antioxidant micronutrient requirements for athletes. To this effect, the training-load interaction with nutrition is taken into account. As oxidative stress cannot be avoided, the imbalance between oxidants and antioxidants can be alleviated to minimise oxidative damage and outcomes. There is growing evidence that one specific antioxidant cannot by itself prevent oxidative stress-induced damage, as direct adverse effects of supplementation are attributed to undesirable synergic effects. Other effects can be supposed that limit the endogenous adaptive effect of training. High doses of antioxidant supplements can minimise the effects of radical oxygen species themselves or generate pro-oxidant effects. Effects are only exhibited when nutritional status is deficient. There are no convincing effects of supplementation in well-trained athletes. Risk/benefit analysis emerges on evidence for an unknown risk of supranutritional intakes, a supposed impairment of adaptive effects and a still unknown long-term risk. Appropriate status can be achieved by a diversified and balanced diet, adapted to specific needs, by awareness of high-density food intakes (avoiding products containing a low density of micronutrients).

Plasma homocysteine is related to folate intake but not training status.

BACKGROUND AND AIM: Lifestyle including intakes of several essential nutrients and physical activity are of particular interest in reducing plasma total homocysteine concentration (tHcy), a risk factor for cardiovascular diseases. The aim of this study was to determine in athletes, whether dietary factors such as intakes of folate, vitamin B6 and B12 were associated with lower plasma tHcy, and whether this depended on daily energy expenditure (EE) and type of physical activity performed (aerobic, anaerobic, intermittent). METHODS: Seventy-four well-trained athletes completed 7-day food and activity records in a cross-sectional study. Blood was sampled on day 8. RESULTS: Percentage of vegetal protein, vitamin B6, and folate intakes were higher and tHcy was lower (1) in athletes with high EE (> 16.72 MJ/d) compared to athletes with lower EE; (2) in aerobic athletes compared to intermittent athletes and sedentary subjects. After backward step by step analysis, folate intake was the only significant variable retained in the model to explain tHcy variability. Moreover, after introducing folate intake as a covariate in ANOVA tests, group effects on tHcy were no longer significant. Nutrient density of folate was inversely correlated to tHcy in athletes (r = -0.33; P = 0.004). CONCLUSION: High energy intake (> 16.72 MJ/d) allows the necessary folate intake (> 500 microg/d) for tHcy decrease to occur, which is moreover favored by aerobic activity. The mechanism underlying low tHcy in relation to high EE could only play a minor role when compared to the effect of dietary folate intake on tHcy.